We propose prospective, longitudinal studies of the relationship between early brain injury and language development from birth to age 5, building on 15 years of research on language and cognitive outcomes in children with congenital left- or right hemisphere injuries (due primarily to pre- or perinatal stroke), using state-of-the-art methods for structural imaging and lesion-symptom mapping. The latter include a new method called Voxel-based Lesion Symptom Mapping (VLSM, Bates et al., Nature: Neuroscience, 2003) developed in our laboratories, which permits graded color maps of the relationship between behavioral measures and lesion sites, applied for the first time to children with lesions. New diffusion-tensor imaging (DTI) methods will be used to examine changes in connectivity that may be attributable to early brain injury and subsequent reorganization. Longitudinal studies of language and related non-linguistic functions will be conducted from 8 to 60 months of age, the period in which most of language is acquired, from the first signs of babbling to the mastery of grammar and discourse. Our previous studies suggest that this period is a "window of plasticity", in which most children with early unilateral injuries start with serious delays, but move into the normal to low-normal range on language measures. In children with congenital, unilateral lesions, we will attempt to extend a series of important and surprising findings regarding the specific lesion sites associated with initial delays in babbling, word comprehension, gesture, word production, and grammar, and to examine the trajectories of language and visual spatial development in children with early focal brain damage. Neuroanatomical correlates of milestones, trajectories, delays and recovery from delay will be established based on 3-dimensional lesion reconstruction, VLSM and DTI. For all children with brain injuries, scans will be obtained at two points: on entry into the study (between 6 and 36 months), and at 5 years of age. These two data points will permit within-subject analyses of the initial state of the system with any changes in neuroanatomy that may be related to lesion type and/or to degrees of success or failure in language development. Scans will also be obtained for age- and gender-matched controls at age 5, permitting an assessment of structural alterations due to early injury and subsequent reorganization, alterations which also may correlate with degree and timing of success in language. The new information gained from these studies will enhance our understanding of the timing of changes associated with plasticity in the developing nervous system, as well as defining associations and dissociations in linguistic and visual spatial development. Knowledge gained in this study may form the basis for more effective interventions to help improve neurodevelopmental outcome of children with brain damage in the future. [unreadable] [unreadable]